The present invention relates to new aldehydes and new processes for producing substantially optically pure sugars using racemic substrates, and to new C-alkyl and N-containing sugars produced using such processes.
Several methods have been used to produce substantially optically pure sugars in the past. For example, enzymatic transformations have been used as alternative methods in enantioselective synthesis. Many useful reactions, particularly those based on the use of hydrolases and oxidoreductases have been demonstrated. Enzyme-catalyzed aldol condensations also have been shown synthetically useful. E.g. Wong, C-H., Whitesides, G. M. J. Org. Chem. 48 (1983) 3199; Wong, C-H., Mazenod, F. P., Whitesides, G. M. Ibid. 3493; Durrwachter, J. R., Drueckhammer, D. G., Nozaki, K., Sweers, H.M., Wong, C-H. J. Am. Chem. Soc. 108 (1986) 7812; Wong, C-H. "Enzymes as Catalysts in Organic Synthesis," Schneider, M. P., Ed. Reidel: Dordrecht (1986) 199; Bednarski, M. D., Waldmann, H. J., Whitesides, G. M. Tetrahedron Lett. 27 (1986) 5807; Reimer, L. M., Conley, D. L. Pompliano, D. L., Frost, J. W. J. Am. Chem. Soc. 108 (1986) 8010; Mocali, A., Aldinucci, D., Paoletti, F. Carbohydr. Res. 143 (1985) 288; Kapusinski, M., Franke, F. P., Flanigan, I., MacLeod, J. K., Williams, J. F. Ibid. 140 (1985) 69; Auge, C., Gautheron, C. J. Chem. Soc., Chem. Commun. (1987) 859; David, S., Auge, C. Pure Appl. Chem. 59 (1987) 1501. Enzymatic syntheses normally are carried out in aqueous solution under mild conditions and with no protection of the functional groups of the substrate.
More than fifteen aldolases have been isolated, each of which catalyzes a distinct type of aldol reaction. Wong, C-H. "Enzymes as Catalysts in Organic Synthesis," Schneider, M. P., Ed. Reidel: Dordrecht (1986) 199. The enzyme fructose 1,6-diphosphate (FDP) aldolase has been used for synthesis of a number of common and uncommon sugars including deoxyhexoses, fluoro sugars, .sup.13 C-labeled sugars, and many high-carbon sugars. The enzyme is specific for dihydroxyacetone phosphate (DHAP) as the aldol donor, but will accept a variety of aldehydes as acceptors. As an alternative to DHAP as the aldol donor, dihydroxyacetone (DHA) along with a catalytic amount of inorganic arsenate may be used. Durrwachter, J. R., Drueckhammer, D. G., Nozaki, K., Sweers, H. M., Wong, C-H. J. Am. Chem. Soc. 108 (1986) 7812. The stereochemistry of the newly formed C--C bond is the same in all aldol reactions studied so far. The chiral environment in the aldehyde acceptors does not affect the stereochemistry of the C--C bond formation.
The major obstacle encountered in enyzmatic aldol condensation is that the preparation of aldehyde acceptors is difficult, particularly if an enantiomerically pure aldehyde is required. Another potential problem is that many interesting .alpha.-substituted chiral aldehydes are not stable in aqueous solution, prohibiting the preparation of many interesting uncommon sugars.